A first-in-human phase I trial of a novel peptide vaccine LabVax 3(22)-23 and adjuvant GM-CSF sargramostim in patients with refractory labyrinthin-expressing adenocarcinomas.
Authors: Tianhong Li, Shuai Chen, Weijie Ma, Kit Wah Tam, Rashmi Verma, Chihong Zhou, Laura Molnar, Leslie A. Garcia, Kris K. Johnston, Kyra Toomey, Dennis J. Montoya, Jie Zeng, Varun R. Viswanath, Colleen A. Pineda, Nancy L. Ogihara, James A. Radosevich, Michael Babich
Journal: Journal of Clinical Oncology (2023)

e14660 Background: Labyrinthin (Lab) is a novel tumor-specific protein expressed on the cell surface of the majority of adenocarcinomas of various cancer types. LabVax 3(22)-23 contains 4 synthetic Lab-based peptides designed to elicit both B-cell and T-cell responses. We hypothesized that vaccination against labyrinthin could elicit strong immune responses against Lab-positive adenocarcinomas in cancer patients (pts). This single institution, first-in-human, phase I trial (UCDCC#296) evaluated the feasibility and safety of LabVax 3(22)-23 and adjuvant GM-CSF sargramostim in pts with Lab-positive metastatic or recurrent adenocarcinoma of any primary tumor site after standard-of-care therapies. Methods: Eligible pts were &gt;18 years of age, had metastatic adenocarcinomas of any histology, Lab expression on their tumor cells by immunohistochemistry, adequate end organ function, and performance status (PS) 0-1. Pts received GM-CSF subcutaneously and LabVax 3(22)-23 intradermally on weeks 1, 2, 4, 8, and 12 in the absence of disease progression or unacceptable toxicity. After completion of study treatment, pts were/are followed every 3 months for 1 year. The primary objective was to assess the toxicity per CTCAE V5.0. Dose limiting toxicity (DLT) was defined as grade ≥ 2 allergic and autoimmune reaction, grade ≥ 3 injection site reaction, any grade 3 toxicities lasting &gt;1 week, or any grade ≥ 4 toxicities. Results: All 10 pts were accrued: median (range) age, 52 (34-73) yrs; female/male, 6/4; White/Asians/Hispanic, 7/2/1; PS 1: 100%. Tumor types included colon or rectum (8), ovarian (1), and scalp (1). Median number (range) of prior line systemic therapies, 4 (1-8). The treatment has been well tolerated without any DLT or drug-related severe adverse effect. As of February 10, 2023, 2 pts completed all 5 treatments with stable disease as the best tumor response, and 1 pt is scheduled for last treatment. Seven pts discontinued treatment early due to tumor progression, 3 pts after 4 treatments and 4 pts after 3 treatments. OS has not matured yet. RNA sequencing analysis of peripheral blood mononuclear cells (PBMCs) of first two pts revealed LabVax 3(22)-23 modulated the activity of immune cells and PD-1 pathway. Other correlative studies are ongoing for the effect of LabVax 3(22)-23 on various immune responses (cytokines, anti-Lab antibody production). Conclusions: LabVax 3(22)-23 and GM-CSF were well tolerated in these heavily pre-treated patients with Lab-expressing, refractory adenocarcinomas. Based on preclinical synergism with pembrolizumab, this dose and injection schedule will be tested in a phase II open label study of LabVax 3(22)-23 and GM-CSF in combination with pembrolizumab in patients with refractory lung adenocarcinomas and adenocarcinomas of all other tumor types. Clinical trial information: NCT051013560 .